Chediak-Higashi syndrome is a genetic disease of children and various animal species including mice. In man the syndrome most commonly terminates in lymphoma-like malignant disease. We showed that this syndrome is associated with impaired microtuble function correctable in vitro and in vivo by agents that elevate cyclic GMP i.e. cholinergic agonists and ascorbic acid. Our research effort will be directed this year toward further analysis of the membrane lipid abnormalities in CH syndrome that may be basic to the microtubule and other defects. We will explore the relationship between microtubule assembly status and cyclic nucleotide levels, emphasizing the possibility that high cyclic AMP in Chediak-Higashi cells is a consequence and not a cause of the microtubule defect. In addition, we plan to compare membrane properties and cytoskeletal organization in cells lacking cytoplasmic microtubules due to malignant transformation, drug treatment (colchicine), genetic disease (Chediak-Higashi syndrome) and stage of the cell cycle (mitosis). Preliminary experiments indicate analogies between the first three conditions which may not extend to mitotic cells.